Wayne State University initiates groundbreaking multiple sclerosis study

A groundbreaking study in multiple sclerosis focusing on “remyelination in the brain” has been initiated by Omar Khan, M.D., professor and chair of neurology at the Wayne State University School of Medicine.

“This is a novel approach in the treatment of multiple sclerosis, which is characterized by diffuse demyelination and axonal loss in the central nervous system,” said Dr. Khan, who also serves as director of the Multiple Sclerosis Center and director of the Sastry Foundation Advanced Imaging Laboratory. “In this study, we are targeting remyelination in the central nervous system.”

Dr. Khan noted that there are 10 United States Food and Drug Administration-approved treatments for multiple sclerosis, none with any well-characterized reparative or remyelinating potential. Those treatments primarily focus on altering the behavior of the immune system and target inflammation.

However, this new approach targets remyelination in the central nervous system using a humanized monoclonal antibody that binds to the semaphorin 4D, a member of the semaphorin family of proteins and an important mediator of axonal growth cone guidance. Semaphorin-induced signaling also has been shown to induce growth cone collapse of neurons and apoptosis of neural precursors, and to induce process extension collapse and apoptosis of oligodendrocytes. Semaphorins consist of a family of soluble and membrane-bound proteins that were originally defined as axonal-guidance factors. These proteins play important roles in establishing precise connections between neurons and their appropriate targets.

“Therefore, it is a plausible target with the realistic goal of achieving remyelination,” Dr. Khan said. “This is a paradigm shift and the start of the next generation of therapies to treat multiple sclerosis that will change its focus to repair rather than inflammation.”

The brain can largely be divided into gray and white areas. Neurons are located in the gray area, and the white parts are where neurons send their axons – similar to electrical cables carrying messages – to communicate with other neurons and bring messages from the brain to muscles. The white parts of the brain are white because a cell type called 

oligodendrocytes makes a cholesterol-rich membrane called myelin that coats the axons.

The myelin’s function is to insulate the axons, similar to the plastic sheath coating electrical cables. In addition, the myelin speeds communication along axons and makes that communication more reliable. In patients with MS, their immune system attacks the myelin sheathing. The subsequent degradation leads to the messages from the brain to other parts of the body leaking and derailing from their intended target.

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